APPLICANT'S ABSTRACT: Breaking the cycle of intergenerational transmission of alcohol dependence from women alcoholics to their offspring through intervention requires identification of relevant mediating and moderating risk/protective factors. Because we need a better understanding of how to identify those children at highest risk, study of offspring of parents with the most severe form of the disorder is needed. We have identified a severe form of alcoholism in women utilizing a "double proband" methodology which was first developed in our laboratory to select more severe cases of male alcoholism (e.g., early onset, high familial aggregation). In comparison to low-risk controls, off-spring from high risk families of alcoholic women display evidence of neurodevelopmental delay (event-related potential differences including reduction in the amplitude of the p300), and more psychopathology, both externalizing and internalizing. The primary goal of the proposed renewal is to follow 200 high and low-risk offspring over the next five years. We will model: (1) age of onset for regular drinking, and (2) severity of psychopathology. In order to insure that the findings to date are robust, we will include an unscreened control group of offspring to be compared with our high-risk group and the screened low-risk group already available for follow-up. The current submission documents the feasibility of finding a sufficient number of offspring from "double proband" families. This has been accomplished by our progress in finding and testing more new high-risk children in the past year than we had originally proposed. By the time the proposed study would be eligible for finding, we will have enrolled over three-quarters of the proposed sample. Initial findings underscore the importance of utilizing potential neurobiological markers prospectively, relating them to later development of alcohol dependence. The possible interplay between environmental variation and the neurobiological factors associated with high-risk status also suggests the need to assess this variation in the context of a longitudinal follow-up.